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Dose-effect analysis of 6-APB ("Benzofury") on fear memory, motor behavior, and reward
Kyla M Whitelock1, Kaitlin R Van Alstyne2,3, Liam J Conaboy2
1Department of Psychology , Molecular Cognition Laboratory, University of California, MC 0109, 9500 Gilman Dr, La Jolla, CA, 92093-0109, USA. kwhitelock@ucsd.edu.
Rationale:
6-(2-aminopropyl)benzofuran (6-APB) is a recreational drug that is structurally similar to MDMA. Very little is known about the behavioral effects of 6-APB or its dose-effect relationship in vivo. As the popularity of new psychoactive substances (NPS), such as 6-APB, increases due to their unscheduled status and easy availability, it is important to understand the potential benefits and/or harms of such substances.
Objectives:
The current study aims to establish a dose-effect curve of 6-APB on fear memory, pain sensitivity, motor coordination, and addiction-related behavior in mice.
Methods:
Male and female hybrid C57BL/6Jx129S1/SvImJ mice were used to examine the effects of 0.01 to 5 mg/kg of 6-APB on Pavlovian fear conditioning; flinch, jump, vocalize; Accelerating Rotarod; behavioral sensitization, conditioned place preference, and conditioned responding.
Results:
We found that 6-APB elicits effects at very low doses (0.01 and 0.1 mg/kg), while impairing short-term fear memory and long-term context memory at a dose of 5 mg/kg. We also observed that 6-APB produces modest locomotor sensitization and may produce addiction. Finally, there is evidence of reduced shock reactivity; this was not likely due to analgesia and more likely due to ataxia produced by the drug.
Conclusions:
6-APB produces a behavioral profile broadly similar to MDMA, with amnesic effects emerging at higher doses than MDMA and a larger gap between potential therapeutic doses and doses that produce cognitive deficits. These findings suggest 6-APB may not be the low-risk therapeutic alternative to MDMA currently sought in clinical contexts, though further research is warranted.
Insights
This study investigated the behavioral effects of 6-(2-aminopropyl)benzofuran (6-APB) in mice. 6-APB shows potential for addiction and cognitive impairment at higher doses, similar to MDMA.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- 6-(2-aminopropyl)benzofuran (6-APB) is a novel psychoactive substance (NPS) structurally related to MDMA.
- Limited data exists on 6-APB's behavioral effects and dose-response relationship in vivo.
- Understanding NPS like 6-APB is crucial due to their increasing popularity and availability.
Purpose of the Study:
- To establish a dose-effect curve for 6-APB.
- To assess 6-APB's impact on fear memory, pain sensitivity, motor coordination, and addiction-related behaviors in mice.
Main Methods:
- Utilized male and female hybrid mice.
- Administered 6-APB at doses ranging from 0.01 to 5 mg/kg.
- Evaluated effects on fear conditioning, pain response, motor coordination (Accelerating Rotarod), behavioral sensitization, conditioned place preference, and conditioned responding.
Main Results:
- 6-APB demonstrated effects at low doses (0.01-0.1 mg/kg).
- Higher doses (5 mg/kg) impaired short-term and long-term fear memory.
- Observed modest locomotor sensitization, potential for addiction, and reduced shock reactivity likely due to ataxia, not analgesia.
Conclusions:
- 6-APB exhibits a behavioral profile similar to MDMA.
- Amnesic effects occur at higher doses compared to MDMA.
- 6-APB may not be a low-risk alternative to MDMA, warranting further investigation.
